Despite recent advances in blood glucose control, the continually rising incidence of diabetes leads to an ever- increasing burden of disease complications. Major limitations to treatment include inability to bioengineer beta cell replacement for both type 1 and 2 diabetes, as well as to monitor and image the development of the disease, and to engineer repair of diabetic tissues. Such advances depend on innovations and discoveries throughout the physical and biological sciences, and the ability to bring these advances to the relevant clinical problems. The following examples describe current relevant challenges that are intimately dependent on advances in basic and translational sciences. (1) Progress in cell therapy and tissue engineering promises major breakthroughs in repair of diabetic tissues, but model systems as well as noninvasive imaging of potential replacement cells will be needed to ascertain delivery to target sites. (2) Novel and hybrid imaging systems need to be developed, including microscopic and macroscopic approaches such as PET and optical or photoacoustic imaging are needed to gain deeper and finer assessment of tissue pathologies. (3) Nanoparticles with multimodality imaging capabilities and drug payloads need to be optimized and moved into clinical trials. To transform diabetes outcomes, these and other challenges must be met by interdisciplinary teams of engineers, physicists, computer scientists, biologists, and physicians working together at the interfaces between biology, technology, and medicine. This program seeks to enable these processes, in order to bring advances in technology and engineering to bear on the challenges of research and translation to improved therapeutic outcome, by training a new generation of researchers with strength in physical science and engineering, and with intimate exposure to and involvement in relevant areas of biomedical research. Dually mentored pre-Doctoral and post-Doctoral researchers will develop and apply novel imaging, modeling (both computational and experimental) and engineering approaches to key questions in diabetes and associated pathologies.